Expired Study
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Chicago, Illinois 60637


Purpose:

This randomized phase II trial is to see if combination chemotherapy works better with or without bevacizumab in treating patients who have malignant mesothelioma. Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or deliver cancer-killing substances to them. It is not yet known if combination chemotherapy works better with or without bevacizumab in treating malignant mesothelioma.


Study summary:

OBJECTIVES: I. Compare the time to progression of patients with malignant mesothelioma treated with gemcitabine and cisplatin with or without bevacizumab. II. Compare the objective response rate in patients treated with these regimens. III. Compare the toxicity of these regimens when administered to these patients. IV. Compare the median and overall survival of patients treated with these regimens. V. Assess plasma vascular endothelial growth factor and serum vascular cell adhesion molecule-1 levels before, during, and after study therapy as predictors of outcome in these patients. OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to histology (epithelial vs other) and ECOG performance status (0 vs 1). Patients are randomized to one of two treatment arms. ARM I: Patients receive gemcitabine IV over 30 minutes on days 1 and 8 and cisplatin IV over 30-60 minutes (beginning after gemcitabine infusion) and bevacizumab IV over 30-90 minutes (beginning after cisplatin infusion) on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve stable disease (SD), complete response (CR), or partial response (PR) after the sixth course may receive bevacizumab as a single agent once every 3 weeks in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive gemcitabine and cisplatin as in arm I and placebo IV over 30-90 minutes (beginning after cisplatin infusion) on day 1. Treatment repeats as in arm I. Patients who achieve SD, CR, or PR after the sixth course may receive placebo as a single agent once every 3 weeks in the absence of disease progression.


Criteria:

Inclusion Criteria: - Histologically or cytologically confirmed malignant pleural or peritoneal mesothelioma that is not amenable to curative surgery - Epithelial, sarcomatoid, or mixed subtype - Evidence of gross unresectability, including, but not limited to, the following conditions: - Direct extension into the chest wall - Mediastinal or hilar lymphadenopathy - Pulmonary or cardiac function that is inadequate to tolerate resection - Sarcomatoid or mixed histology - Pleural mesothelioma must be stage II or greater using the International Mesothelioma Interest Group staging system - Measurable disease outside prior irradiation port - At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan - Pleural effusions and ascites are not considered measurable lesions - Site in pleura, lung, liver, or retroperitoneum that can be assessed by MRI for evaluation of blood flow - No obvious tumor involvement of major vessels by CT scan - No known brain metastases - Performance status - ECOG 0-1 - More than 3 months - WBC at least 3,000/mm^3 - Absolute neutrophil count at least 1,500/mm^3 - Platelet count at least 100,000/mm^3 - No history of bleeding diathesis - Bilirubin normal - AST/ALT no greater than 2.5 times upper limit of normal - INR no greater than 1.5 - Creatinine no greater than 1.5 mg/dL - Creatinine clearance at least 60 mL/min - If 1+ or greater proteinuria on dipstick, then must have less than 500 mg of protein/24-hour urine collection - No significant renal impairment - See Disease Characteristics - No history deep vein thrombosis - No myocardial ischemia or infarction within the past 6 months - No uncompensated coronary artery disease within the past 6 months - No uncontrolled hypertension - No symptomatic congestive heart failure - No unstable angina pectoris within the past 6 months - No cardiac arrhythmia - No transient ischemic attack within the past 6 months - No cerebrovascular accident within the past 6 months - No other arterial thromboembolic event within the past 6 months - No clinically significant peripheral artery disease - See Disease Characteristics - No history of pulmonary embolism - No prior allergic reactions attributed to compounds of similar chemical or biologic composition to bevacizumab or other study agents - No other active malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix - No ongoing or active infection - No other concurrent uncontrolled illness that would preclude study participation - No psychiatric illness or social situations that would preclude compliance - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception - No growth factors for 24 hours before, during, or for 24 hours after cytotoxic chemotherapy - See Biologic therapy - Prior intrapleural cytotoxic agents (including bleomycin) allowed - No prior systemic cytotoxic chemotherapy - See Disease Characteristics - At least 4 weeks since prior radiotherapy and recovered - See Disease Characteristics - At least 6 weeks since prior major surgery - At least 30 days since prior investigational drug - No other concurrent investigational or commercial agents or therapies - No concurrent combination antiretroviral therapy for HIV-positive patients


Study is Available At:


Original ID:

NCI-2012-02430


NCT ID:

NCT00027703


Secondary ID:

NCI-2012-02430


Study Acronym:


Brief Title:

Combination Chemotherapy With or Without Bevacizumab in Treating Patients With Malignant Mesothelioma


Official Title:

A Double Blind, Placebo Controlled Randomized Phase II Trial Of Gemcitabine And Cisplatin With Or Without The VEGF Inhibitor Bevacizumab (NSC #704865) In Patients With Malignant Mesotheloma


Overall Status:

Completed


Study Phase:

Phase 2


Genders:

Both


Minimum Age:

18 Years


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

National Cancer Institute (NCI)


Oversight Authority:

United States: Food and Drug Administration


Reasons Why Stopped:


Study Type:

Interventional


Study Design:

Allocation: Randomized, Endpoint Classification: S


Number of Arms:

2


Number of Groups:

0


Total Enrollment:

106


Enrollment Type:

Actual


Overall Contact Information

Official Name:Hedy Kindler
Principal Investigator
University of Chicago

Study Dates

Start Date:October 2001
Primary Completion Date:May 2006
Primary Completion Type:Actual
Verification Date:December 2012
Last Changed Date:February 10, 2014
First Received Date:December 7, 2001

Study Outcomes

Outcome Type:Secondary Outcome
Measure:Incidence of adverse events graded according to NCI CTCAE version 3.0
Time Frame:Up to 9 years
Safety Issues:True
Description:Toxicity rates will be compared between the two groups via chi-square or Fisher exact tests.
Outcome Type:Secondary Outcome
Measure:Overall survival
Time Frame:Up to 9 years
Safety Issues:False
Description:Kaplan-Meier estimates of overall survival rates will be derived and compared between the two groups using a stratified log-rank test.
Outcome Type:Secondary Outcome
Measure:Rate of disease stabilization
Time Frame:Up to 6 months
Safety Issues:False
Description:Will be compared between groups using chi-square or Fisher exact tests, as appropriate.
Outcome Type:Secondary Outcome
Measure:Objective response rate (complete and partial response)
Time Frame:Up to 6 months
Safety Issues:False
Description:Will be compared between groups using chi-square or Fisher exact tests, as appropriate.
Outcome Type:Secondary Outcome
Measure:Complete response rate
Time Frame:Up to 6 months
Safety Issues:False
Description:Will be compared between groups using chi-square or Fisher exact tests, as appropriate.
Outcome Type:Primary Outcome
Measure:Time to disease progression
Time Frame:Time from randomization until the first evidence of progression, up to 9 years
Safety Issues:False
Description:The two treatment groups will be compared using a stratified logrank test. Kaplan-Meier time-to-event curves will be constructed for each treatment group. Median time-to-progression in each group and corresponding 95% confidence intervals will be derived

Study Interventions

Intervention Type:Drug
Name:gemcitabine hydrochloride
Description:Given IV
Arm Name:Arm I
Other Name:dFdC
Intervention Type:Drug
Name:cisplatin
Description:Given IV
Arm Name:Arm I
Other Name:CACP
Intervention Type:Biological
Name:bevacizumab
Description:Given IV
Arm Name:Arm I
Other Name:anti-VEGF humanized monoclonal antibody
Intervention Type:Other
Name:placebo
Description:Given IV
Arm Name:Arm II
Other Name:PLCB
Intervention Type:Other
Name:laboratory biomarker analysis
Description:Correlative studies
Arm Name:Arm I

Study Arms

Study Arm Type:Experimental
Arm Name:Arm I
Description:Patients receive gemcitabine IV over 30 minutes on days 1 and 8 and cisplatin IV over 30-60 minutes (beginning after gemcitabine infusion) and bevacizumab IV over 30-90 minutes (beginning after cisplatin infusion) on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve stable disease (SD), complete response (CR), or partial response (PR) after the sixth course may receive bevacizumab as a single agent once every
Study Arm Type:Experimental
Arm Name:Arm II
Description:Patients receive gemcitabine and cisplatin as in arm I and placebo IV over 30-90 minutes (beginning after cisplatin infusion) on day 1. Treatment repeats as in arm I. Patients who achieve SD, CR, or PR after the sixth course may receive placebo as a single agent once every 3 weeks in the absence of disease progression.

Study Agencies

Agency Class:NIH
Agency Type:Lead Sponsor
Agency Name:National Cancer Institute (NCI)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Results Reference
Citation:Kindler HL, Karrison TG, Gandara DR, Lu C, Krug LM, Stevenson JP, Jänne PA, Quinn DI, Koczywas MN, Brahmer JR, Albain KS, Taber DA, Armato SG 3rd, Vogelzang NJ, Chen HX, Stadler WM, Vokes EE. Multicenter, Double-Blind, Placebo-Controlled, Randomized Phase II Trial of Gemcitabine/Cisplatin Plus Bevacizumab or Placebo in Patients With Malignant Mesothelioma. J Clin Oncol. 2012 Jun 4. [Epub ahead of print]
PMID:22665541
Reference Type:Results Reference
Citation:Kindler HL, Karrison T, Lu C, et al.: A multicenter, double-blind, placebo-controlled randomized phase II trial of gemcitabine/cisplatin (GC) plus bevacizumab (B) or placebo in patients (pts) with malignant mesothelioma (MM). [Abstract] J Clin Oncol 23 (Suppl 16): A-7019, 625s, 2005.

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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